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HistologyTypes of tissuesCartilage and boneBone formation: Ossification
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HistologyTypes of tissuesCartilage and boneBone formation: Ossification

Bone formation: Ossification

Author: Julie Doll, MSc • Reviewer: Dimitrios Mytilinaios, MD, PhD
Last reviewed: October 30, 2023
Reading time: 8 minutes

Bone formation in a developing embryo begins in mesenchyme and occurs through one of two processes: either endochondral or intramembranous osteogenesis (ossification). Intramembranous ossification is characterized by the formation of bone tissue directly from mesenchyme. Flat bones, such as the parietal and occipital bones, are formed using this process.

On the contrary, endochondral ossification is dependent on a cartilage model. Long and short bones, such as the femur and phalanges, arise from a cartilage model formed by endochondral ossification. The distinction between these two types of osteogenesis does not imply the existence of multiple types of bone tissue.

Both processes result in the same bone tissue; however, they are distinguished by the presence or absence of a cartilage model.

Contents
  1. Intramembranous ossification
  2. Endochondral ossification
    1. Primary ossification center
    2. Secondary ossification center
  3. Growth in length
  4. Bone remodeling
  5. Bone repair
  6. Sources
+ Show all

Intramembranous ossification

Intramembranous ossification forms flat and irregular bones. In this process, mesenchymal cells differentiate directly into osteoblasts; specialized cells that secrete bone matrix. As the osteoblasts are housed within the matrix they secrete, they become progressively distanced from each other but remain connected through thin cytoplasmic processes.

Bone matrix (histological slide)

The osteoblasts differentiate into osteocytes and their processes are enclosed within canaliculi as the matrix becomes calcified. As the bone tissue develops, osteoblasts create a network of trabeculae and spicules.

Osteoblasts (histological slide)

Concurrently, more surrounding mesenchymal cells differentiate into osteoprogenitor cells and come into contact with newly formed bone spicules. These cells will become osteoblasts, secrete more matrix, and continue to generate bone. This process is referred to as appositional growth.

Intramembranous ossification (histological slide)

Endochondral ossification

Primary ossification center

  • First, a cartilage model of the bone is formed; mesenchymal cells condense and differentiate into chondrocytes, forming the hyaline cartilage model.   The chondrocytes hypertrophy and the extracellular matrix surrounding them becomes calcified.
Chondrocytes (histological slide)
  • Blood vessels invade the center of the cartilage model and cause the perichondrium to differentiate into periosteum. As this occurs, chondrogenic cells convert to osteoprogenitor cells.
Periosteum (histological slide)
  • Osteoprogenitor cells then convert to osteoblasts.
  • Bone matrix secreted by the osteoblasts forms a bone collar. The bone collar prevents nutrients from reaching the hypertrophied chondrocytes, causing them to degenerate.
  • Osteoclasts, cells that break down bone, arrive and form holes in the bone collar allowing the passage of periosteal buds. Periosteal buds consist of blood vessels, osteoprogenitor cells, and hemopoietic cells.
  • Osteoprogenitor cells brought to the developing bone through the periosteal buds divide, forming more osteoprogenitor cells. Some of these cells will differentiate into osteoblasts that will continue to form bone matrix on the surface of the calcified cartilage.
  • As the bone matrix calcifies, it forms the calcified cartilage-calcified bone complex
  • The bone collar continues to grow in either direction towards the epiphyses and osteoclasts resorb the calcified cartilage-calcified bone complex to widen the marrow cavity.
Primary ossification center (histological slide)

Secondary ossification center

Secondary ossification centers are found at the epiphyses of long bones. This process is similar to that of the primary center of ossification, but occurs without a bone collar. Instead, osteoprogenitor cells enter the epiphyseal cartilage, differentiate into osteoblasts, and secrete matrix on the cartilage framework. Long bones increase in length at the secondary ossification centers.

Growth in length

Bone growth in length occurs at the epiphyses. Under a microscope, five zones of ossification can be readily seen in the epiphyses.

  • Zone of reserve cartilage – This zone, farthest from the diaphysis, is characterized by randomly arranged, mitotically active chondrocytes.
Zone of reserve cartilage (histological slide)
  • Zone of proliferation – Chondrocytes are proliferating and form isogenous groups in rows oriented parallel to the long axis of the bone.
Zone of proliferation (histological slide)
  • Zone of hypertrophy – Here the cells move toward the diaphysis, hypertrophy, mature, and collect glycogen within their cytoplasm. As they are migrating, the chondrocytes undergo apoptosis.
Zone of maturation and hypertrophy (histological slide)
  • Zone of calcification – Calcium ions brought to the epiphysis through blood vessels calcify the cartilage matrix surrounding the dying chondrocytes. Although it is calcified, this is not yet bone tissue.
Zone of calcified cartilage (histological slide)
  • Zone of ossification – In this zone, osteoprogenitor cells arrive and become osteoblasts. The osteoblasts secrete bone matrix on the calcified cartilage. Bone tissue is formed here as the matrix becomes calcified.

Bone remodeling

Bone remodeling is a balance between bone resorption and deposition that maintains the shape of a bone as stresses are placed on it. Developing bones maintain the same general shape through surface remodeling. In this process bone is deposited under certain regions of the periosteum while it is being resorbed in others. Simultaneously, bone is being deposited and resorbed in various regions of the endosteal surface. The rate of deposition and resorption in any area alters or maintains the shape of the bone.

Osteoclasts (histological slide)

The internal structure of bone is continuously altered in response to weight changes, microfractures, and changes in posture. This process is referred to as internal remodeling and is carried out by a bone remodeling unit. The unit is made up of a cutting cone and a closing cone. The cutting cones are cone shaped tunnels formed in the compact bone by osteoclasts recruited to resorb bone tissue. Blood vessels, osteoblasts, and osteoprogenitor cells enter the cutting cones when the tunnels reach their maximum diameter. When this occurs, bone resorption stops and osteoblasts begin depositing new lamellae around the blood vessels. These new Haversian systems are the closing cones.

Haversian canal (histological slide)

Bone repair

Fractures in bones damage the bone matrix, tear periosteum and endosteum, kill cells, and sometimes displace the ends of the broken bone. Severed blood vessels near the fracture fill the area around the break with blood and form a clot. Capillaries and fibroblasts form connective tissue near the fracture, invade the clot, and form granulation tissue.

Increased mitotic activity in the osteogenic layer of the periosteum results in the buildup of osteoprogenitor cells approximately 48 hours following injury. The osteoprogenitor cells nearest to the bone differentiate into osteoblasts and form a bone collar cemented to the dead bone near the fracture. Because the proliferation of osteoprogenitor cells is more rapid than that of the capillaries, the cells in the center of the proliferating cluster do not receive sufficient blood supply and become chondrogenic cells. The resulting chondrogenic cells differentiate into chondroblasts that form cartilage in the superficial areas of the bone collar. The more superficial layer of osteoprogenitor cells has a profuse blood supply and therefore continues to proliferate. This gives the bone collar three blended zones:

  1. Superficial layer of proliferating osteoprogenitor cells
  2. Middle layer of cartilage
  3. Deep layer of new bone forming on the fragmented bone

Concurrently, the bone collars on either ends of the fragments fuse and form a single collar referred to as an external callus. The cartilage matrix near the deep layer of the external collar becomes calcified. It will then be replaced with cancellous (spongy) bone. By the end of repair, endochondral ossification will convert all of the cartilage into primary bone tissue.

Sources

All content published on Kenhub is reviewed by medical and anatomy experts. The information we provide is grounded on academic literature and peer-reviewed research. Kenhub does not provide medical advice. You can learn more about our content creation and review standards by reading our content quality guidelines.

References:

  • L. P. Gartner: Textbook of Histology, 4th edition, Elsevier (2017) p. 155, 164-172
  • M. H. Ross: Histology: A Text and Atlas, 6th edition, Lippincott Williams & Wilkins (2011), p. 232-238
  • T. W. Sadler: Medical Embryology, 12th edition, Lippincott Williams & Wilkins (2012) p.133-135

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